DESCRIPTION: The proposal details a novel means of meeting the challenge of antibiotic resistance of pathogenic organisms. It is based on the assumption that genomic information for the pathogen of interest is complete enough to permit useful probabilities of finding weak points to exploit. The goal of the proposal is to determine the sensitivity of the organism to deletion of individual genes or relatively small groups of genes. In this way it is hoped to find deletions which are lethal to the organism but at the same time harmless for the human host. At a more detailed level the proposal lays out mathematical procedures for finding lethal deletions and for putting the results in convenient form for the investigator. Only computer simulations will be made, and it is not expected to find any promising new antibiotics. Rather the proposal is to investigate the feasibility and potential utility of the procedures outlined.